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MP25-07 PROSTATIC INFLAMMATION EVOKES UPREGULATION OF NEUROTROPHINS IN SENSORY GANGLIA: POSSIBLE CONTRIBUTION TO DYSFUNCTIONAL VOIDING
THE JOURNAL OF UROLOGYâ
Vol. 193, No. 4S, Supplement, Saturday, May 16, 2015
MP25-06 MODELS OF LOWER URINARY TRACT SYMPTOMS IN THE PRESENCE AND ABSENCE OF PAIN Daniel J. Mazur*, Anthony J. Schaeffer, Praveen Thumbikat, Chicago, IL INTRODUCTION AND OBJECTIVES: Chronic prostatitis/ chronic pelvic pain syndrome (CP/CPPS) is a debilitating condition characterized mainly by pelvic pain. In addition, many patients report voiding complaints and lower urinary tract symptoms (LUTS). While the mechanism behind these voiding complaints is not well understood, it is possible that inflammation induces fibrosis within the prostate, as has been hypothesized to occur in benign prostatic hyperplasia (BPH). To better understand this process, we developed two transient infectioninduced prostatitis murine models where LUTS can be studied in the presence or absence of chronic pain. METHODS: C57BL/6 (B6) and NOD/ShiLtJ (NOD) mice (5-7 weeks old) were transurethrally infected with Escherichia coli strain CP1, a bacteria from a CP/CPPS patient that clears from the prostate and bladder of mice by 30 days. At post-infection days 5, 14, and 35, the mice were pain tested for referred pain with von-Frey filaments and the prostates and bladders harvested for analysis (4-8 mice per time point). Additionally, urodynamic evaluation was completed at day 35 under urethane anesthesia. Prostate and bladder specimens were analyzed by flow cytometry and real-time quantitative PCR (QT-PCR) for the presence of cells and markers involved in fibrosis. RESULTS: B6 mice did not develop pain, however, NOD mice developed significant pain at all time points. Cystometry showed increased frequency of bladder contractions in CP-1 infected mice of both strains. By flow cytometry, B6 mice developed an increase in fibrocytes (vimentinþ, CD45þ) in the prostate at day 14 which became statistically significant at day 35. A similar but delayed trend was noted in NOD mice with an increase in fibrocytes at day 35, however, this was not statistically significant. NOD mice did develop a significant increase in vimentinþ cells (mesenchymal cells) at day 14. The bladders of B6 mice demonstrated a significant increase in vimentinþ cells at day 35 and at day 14 in the NOD mice. There was no difference in the presence of fibrocytes in the bladders. B6 mice had a >1 fold increase in expression of collagen 1a1, 1a2, aSMA, and CXCL5 at day 14 by QTPCR. A similar increase in these markers was noted in the NOD mice but at the earlier time point of day 5. CONCLUSIONS: We have demonstrated in infection-induced prostatitis murine models that urinary frequency develops in the presence and absence of pain. This is associated with the concurrent suggestion of fibrosis within the prostate, with altered kinetics of development in each model. Further studies are underway to identify the pathogenesis of LUTS in the context of inflammation and pain.
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groups was harvested on the 7th day for protein expression of nerve growth factor (NGF), and brain derived neurotrophic factor (BDNF). RESULTS: Frequent urination and reduced voided volume was observed on the 7day in NIP group compared to sham. Expression of NGF and BDNF was significantly upregulated in L6-S1 DRG of NIP group relative to sham (*p<0.05; n¼3 see fig.), whereas expression of neurotrophins in the mid-cervical ganglia of two groups was indifferent. Only NGF was significantly unregulated in prostate of NIP group (82.70 12.76 vs 34.69 10.41 pg per mg of protein, n¼3), and BDNF was slightly elevated in NIP prostate. Expression of NGF and BDNF was similar in bladder of two groups. CONCLUSIONS: Results suggest that prostatic inflammation induces overexpression of BDNF and NGF in L6 and S1 DRG. Afferent axons from prostate or bladder do not innervate midcervical ganglia and its expression of neurotrophins remained unchanged. Phenotypic changes in sensory afferents induced by neurotrophins might mediate the long-lasting functional alterations including dysfunctional voiding that characterize this model of prostatitis.
Source of Funding: None
MP25-07 PROSTATIC INFLAMMATION EVOKES UPREGULATION OF NEUROTROPHINS IN SENSORY GANGLIA: POSSIBLE CONTRIBUTION TO DYSFUNCTIONAL VOIDING
Source of Funding: P20 DK090919
Pradeep Tyagi*, Mahendra Kashyap, Subrata Pore, Zhou Wang, Naoki Yoshimura, Pittsburgh, PA
MP25-08 INTRODUCTION AND OBJECTIVES: Prostatic inflammation is associated with dysfunctional voiding in patients and in animal models. Sensitization of dorsal root ganglia (DRG) neurons is considered an important mechanism underlying voiding dysfunction. Here, we investigated the expression of neurotrophins in dorsal root ganglia (DRGs) receiving innervation from the prostate and bladder in rat model of Noninfectious prostatitis (NIP). METHODS: A single inflammatory insult was given by intraprostatic injection of formalin(50mL) or saline (sham) in three-month-old male Sprague-dawley rats to induce NIP.12 hour night time urination pattern were noted in metabolic cage a day before injection and 7 days later. Tissue from prostate, bladder and dorsal root ganglia of the two rat
EVALUATION OF THE UTILITY OF DIFFERENT SCORING SYSTEMS (FGSI, LRINEC AND NLR) IN THE MANAGEMENT OF FOURNIER’S GANGRENE Ozan Bozkurt, Volkan Sen, Omer Demir, Adil Esen*, Izmir, Turkey INTRODUCTION AND OBJECTIVES: Fournier’s gangrene is still a lethal disease despite recent developments in the area of medicine. Aim of this study is to evaluate the mortality and morbidity prediction capability of three different scoring systems; Fournier’s Gangrene Severity Index (FGSI), Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) and neutrophile-lymphocyte ratio (NLR).
Vol. 193, No. 4S, Supplement, Saturday, May 16, 2015
MP25-06 MODELS OF LOWER URINARY TRACT SYMPTOMS IN THE PRESENCE AND ABSENCE OF PAIN Daniel J. Mazur*, Anthony J. Schaeffer, Praveen Thumbikat, Chicago, IL INTRODUCTION AND OBJECTIVES: Chronic prostatitis/ chronic pelvic pain syndrome (CP/CPPS) is a debilitating condition characterized mainly by pelvic pain. In addition, many patients report voiding complaints and lower urinary tract symptoms (LUTS). While the mechanism behind these voiding complaints is not well understood, it is possible that inflammation induces fibrosis within the prostate, as has been hypothesized to occur in benign prostatic hyperplasia (BPH). To better understand this process, we developed two transient infectioninduced prostatitis murine models where LUTS can be studied in the presence or absence of chronic pain. METHODS: C57BL/6 (B6) and NOD/ShiLtJ (NOD) mice (5-7 weeks old) were transurethrally infected with Escherichia coli strain CP1, a bacteria from a CP/CPPS patient that clears from the prostate and bladder of mice by 30 days. At post-infection days 5, 14, and 35, the mice were pain tested for referred pain with von-Frey filaments and the prostates and bladders harvested for analysis (4-8 mice per time point). Additionally, urodynamic evaluation was completed at day 35 under urethane anesthesia. Prostate and bladder specimens were analyzed by flow cytometry and real-time quantitative PCR (QT-PCR) for the presence of cells and markers involved in fibrosis. RESULTS: B6 mice did not develop pain, however, NOD mice developed significant pain at all time points. Cystometry showed increased frequency of bladder contractions in CP-1 infected mice of both strains. By flow cytometry, B6 mice developed an increase in fibrocytes (vimentinþ, CD45þ) in the prostate at day 14 which became statistically significant at day 35. A similar but delayed trend was noted in NOD mice with an increase in fibrocytes at day 35, however, this was not statistically significant. NOD mice did develop a significant increase in vimentinþ cells (mesenchymal cells) at day 14. The bladders of B6 mice demonstrated a significant increase in vimentinþ cells at day 35 and at day 14 in the NOD mice. There was no difference in the presence of fibrocytes in the bladders. B6 mice had a >1 fold increase in expression of collagen 1a1, 1a2, aSMA, and CXCL5 at day 14 by QTPCR. A similar increase in these markers was noted in the NOD mice but at the earlier time point of day 5. CONCLUSIONS: We have demonstrated in infection-induced prostatitis murine models that urinary frequency develops in the presence and absence of pain. This is associated with the concurrent suggestion of fibrosis within the prostate, with altered kinetics of development in each model. Further studies are underway to identify the pathogenesis of LUTS in the context of inflammation and pain.
e287
groups was harvested on the 7th day for protein expression of nerve growth factor (NGF), and brain derived neurotrophic factor (BDNF). RESULTS: Frequent urination and reduced voided volume was observed on the 7day in NIP group compared to sham. Expression of NGF and BDNF was significantly upregulated in L6-S1 DRG of NIP group relative to sham (*p<0.05; n¼3 see fig.), whereas expression of neurotrophins in the mid-cervical ganglia of two groups was indifferent. Only NGF was significantly unregulated in prostate of NIP group (82.70 12.76 vs 34.69 10.41 pg per mg of protein, n¼3), and BDNF was slightly elevated in NIP prostate. Expression of NGF and BDNF was similar in bladder of two groups. CONCLUSIONS: Results suggest that prostatic inflammation induces overexpression of BDNF and NGF in L6 and S1 DRG. Afferent axons from prostate or bladder do not innervate midcervical ganglia and its expression of neurotrophins remained unchanged. Phenotypic changes in sensory afferents induced by neurotrophins might mediate the long-lasting functional alterations including dysfunctional voiding that characterize this model of prostatitis.
Source of Funding: None
MP25-07 PROSTATIC INFLAMMATION EVOKES UPREGULATION OF NEUROTROPHINS IN SENSORY GANGLIA: POSSIBLE CONTRIBUTION TO DYSFUNCTIONAL VOIDING
Source of Funding: P20 DK090919
Pradeep Tyagi*, Mahendra Kashyap, Subrata Pore, Zhou Wang, Naoki Yoshimura, Pittsburgh, PA
MP25-08 INTRODUCTION AND OBJECTIVES: Prostatic inflammation is associated with dysfunctional voiding in patients and in animal models. Sensitization of dorsal root ganglia (DRG) neurons is considered an important mechanism underlying voiding dysfunction. Here, we investigated the expression of neurotrophins in dorsal root ganglia (DRGs) receiving innervation from the prostate and bladder in rat model of Noninfectious prostatitis (NIP). METHODS: A single inflammatory insult was given by intraprostatic injection of formalin(50mL) or saline (sham) in three-month-old male Sprague-dawley rats to induce NIP.12 hour night time urination pattern were noted in metabolic cage a day before injection and 7 days later. Tissue from prostate, bladder and dorsal root ganglia of the two rat
EVALUATION OF THE UTILITY OF DIFFERENT SCORING SYSTEMS (FGSI, LRINEC AND NLR) IN THE MANAGEMENT OF FOURNIER’S GANGRENE Ozan Bozkurt, Volkan Sen, Omer Demir, Adil Esen*, Izmir, Turkey INTRODUCTION AND OBJECTIVES: Fournier’s gangrene is still a lethal disease despite recent developments in the area of medicine. Aim of this study is to evaluate the mortality and morbidity prediction capability of three different scoring systems; Fournier’s Gangrene Severity Index (FGSI), Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) and neutrophile-lymphocyte ratio (NLR).